Zn2+ is the second most abundant heavy metal ion in biological systems. The average adult human body contains 2.3 g of zinc compared with 4 g of iron. More that 300 enzymes are now known to have zinc in their structure. A major class of eukaryotic transcription factors,, the zinc- finger proteins, contain zinc as a cofactor. The presence of Zn2+ at the active site of enzymes involved in DNA replication and reverse transcription added to the a ttention of biologists to this metal ion. Up regulation of the expression of Zn-binding proteins, particularly of metallothioneins, by Zn2+ is a well-known and well-characterized phenomenon in biology. Zinc appears to play significant role in manipulating the biology of the human parasite, Leishmania. The goal of the proposed research is to understand the regulatory roles of Zn2+ in gene expression, particularly in lower eukaryotes, using Leishmania as a model system. Specific aims of the proposed project are: 1. To understand the influence of Zn2+ in gene expression in Leishmania by ,RNA differential display analysis. 2. To clone and characterize genes that are differentially displayed in Zn-treated Leishmania cells. Genes like metallothionein or super oxide dismutase could be example of genes that are up-regulated by zinc ions. The surface metalloproteinase gene of Leishmania has recently been found to be down regulated by Zn2+. This proposed study should uncover many other novel Leishmania genes that are regulated by zinc ions.